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SymptomAssessmentinSchizophrenicProdromalStates

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SYMPTOM ASSESSMENT IN SCHIZOPHRENICPRODROMAL STATES

Tandy J. Miller, Ph.D., Thomas H. McGlashan, M.D.,Scott W. Woods, M.D., Kelly Stein, Ph.D., Naomi Driesen, Ph.D.,

Cheryl M. Corcoran, M.D., Ralph Hoffman, M.D., andLarry Davidson, Ph.D.

Individuals who develop schizophrenia often suffer long standing deficits. All toooften available treatments remain palliative and do not improve the long-termcourse of illness. The neurobiological deficits associated with the onset of schizo-phrenia may be most active and damaging in the early stages of this life longillness, a fact which has shifted the focus of research and clinical work towardthe early or prodromal stages of this disorder. Results from limited studies sug-gest that early intervention may lead to a better prognosis. Early interventionsthat could delay or prevent the onset of psychotic illnesses have obvious publichealth implications and rely on being able to identify true prodromal patients.The Structured Interview for Prodromal Symptoms and the Scale of ProdromalSymptoms are assessment instruments developed for operationally defining di-agnosis and for quantitatively rating symptom severity for patients prodromalfor psychosis.

INTRODUCTION

Individuals who develop psychotic disorders, such as schizophre-nia, often suffer severe losses in neurobiological functioning and

All authors are affiliated with Yale Medical School.Address correspondence to Tandy J. Miller, Ph.D., Yale Psychiatric Institute,

P.O. Box 208038, New Haven, CT 06520-8038.

PSYCHIATRIC QUARTERLY, Vol. 70, No. 4, Winter 19990033-2720/99/1200-0273$16.00/0 © 1999 Human Sciences Press, Inc. 273

deterioration in quality of life (1). Although current treatments,such as antipsychotic medication, family support, psychoeduca-tion, and continuity of care have proven to be effective in outcomestudies, these treatments remain palliative and usually do notimprove the long-term course of the disease (2). Once individualsdevelop a psychotic illness, they struggle with chronic deficits andremain vulnerable to relapse throughout their lifespan. Unknown,but often irreversible, neurobiological deficit processes are associ-ated with the development of this disorder, are often responsiblefor major losses of functioning, and are understood to be mostactive in the earliest stages of these life long illnesses (3). Accord-ingly, research very recently has shifted focus to the early courseof disorder.

One of the most consistent correlations from this perspectivehas been that the earlier post-onset individuals receive neurolep-tic treatment, the better their short and long term prognosis(4-11). A few clinical research studies have explored whether in-tervention prior to onset, in the prodromal stage of the illness,may alter the natural course of the disorder. One study appliedfamily psychoeducation, long-term monitoring, and conservativelyprescribed antipsychotic treatments to patients who were judgedto be in a prodromal phase of a psychotic illness in an EnglishCounty (12,13). The initiative was associated with a dramaticdrop in the rate of schizophrenia from 7.4 to 0.75 per 100,000people per year during the four years of the study, suggesting thatearly intervention at a prodromal or pre-psychotic stage of illnesscould prevent or delay the onset of full-blown psychosis.

Researchers from Australia have organized programs in thelast 5 years that focus on the early course of psychosis (14,15).Most recently this group has developed a program for assessingand treating young people believed to be at imminent risk for thedevelopment of psychosis. In fact when they followed these youngpeople whom they had diagnosed as prodromal for psychosis, 40%of their sample became psychotic within one year of evaluation(16).

To accomplish this highly successful rate of identification of pro-dromal patients, they operationally defined three states of theprodrome that appear to have predictive validity and power (16-18). Group 1 patients report nonspecific anxiety and/or depressivesymptoms, a recent loss of at least 30 Global Assessment of Func-

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tioning (19) points, and a first degree relative diagnosed with aDSM IV (20) schizophrenia spectrum disorder. Group 2 patientsreport recent onset of at least one attenuated psychotic symptomfrom the DSM IV Schizotypal Personality Disorder criteria ofideas of reference, odd beliefs or magical thinking, perceptualdisturbance, odd thinking and speech, paranoid ideation, and be-havior or appearance. Group 3 patients demonstrate transientpsychotic symptoms including hallucination, delusion, or disorga-nized speech for less than one week before spontaneous reso-lution.

The Australian investigators followed this operational defini-tion, of prodromal patients at high risk for onset, with a clinicaltrial of antipsychotic and psychosocial treatment versus no treat-ment in the same type of sample. By July of 1998, approximately20 patients had been randomized to each cell and twice as manypatients from the no treatment group had converted to psychosis(McGorry, Personal Communication, July, 1998). Though prelimi-nary, these data highlight a new potential for prevention in psy-chosis. The foundation of this pivotal development has been theability to operationally define a truly high risk prodromal patient.This work represents a paradigmatic shift to research focused onthe pre-psychotic phase of schizophrenia. Prior to this, pre-onsettreatment was not considered feasible or ethical because the pro-dromal phase was too nonspecific and the risk/benefit ratio oftreatment was tilted too much toward risk.

These efforts at the very early application of existing treat-ments for schizophrenia have provided enough scientifically com-pelling and therapeutically promising evidence to support a clini-cal trial that is currently being conducted at Yale University'sPRIME Research Clinic (Prevention through Risk Identification,Management, and Education). The aim of the research is to testactive medication (one of the new, atypical antipsychotics) versusplacebo in delaying or averting the transition from a prodromalstate to a full blown, psychotic episode. Modeled after the Austra-lian description of prodromal types, a diagnostic semi-structuredinterview, the Structured Interview for Prodromal Symptoms(SIPS), and a severity scale, the scale of Prodromal Symptoms(SOPS), have been designed to define, diagnose, and measurechange systematically in individuals who may be in a pre-psy-chotic state (21).

TANDY J. MILLER ET AL. 275

The double blind placebo structure of The PRIME preventionclinical trial provides an opportunity to study a population that,with the exception of the current Australian research, has neverbeen studied prospectively. The symptom scores from the SOPScan be tested for their value in predicting the individuals who goon to convert to a frank psychotic disorder. The examination ofthese illnesses while they are developing is particularly importantbecause the participants, their families and others around theseindividuals are likely to be frightened and to distort retrospectiveaccounts of the pre-onset stage of the illness. In addition, thegrowing acknowledgement of clinicians and researchers regardingthe importance of this stage of the illness, has fuelled the need tooperationalize the description of these patients.

Early interventions that may delay or prevent the onset of psy-chotic illnesses and their devastating effects have obvious publichealth implications. These strategies rely on being able to identifytrue positive prodromal patients. The SIPS and the SOPS are di-rected toward extending the progress made by the Australian re-searchers who have provided a beginning prodromal nosology pre-dictive of schizophrenia.

SCALE DEVELOPMENT AND DESCRIPTION

In developing these instruments, available descriptions were re-viewed that used retrospective and prospective assessments tocharacterize or identify the prodromal state. (17, 18, 22-24). Thescales were organized thematically to develop operational defini-tions and rating anchors for the prodromal stages and psychosis.The current instrument is modeled after the Positive and Nega-tive Syndrome Scale (PANSS) (25) with modifications of the posi-tive symptom scales to provide more breadth and detail of scoringwithin the lower, pre-psychotic, ranges of severity. The first goalof the SIPS and the SOPS is to provide a systematic measure ofthe presence/absence of prodromal states as outlined above by theAustralians. The second goal is to measure the severity of prodro-mal symptoms cross-sectionally and longitudinally, and the thirdgoal is to define the threshold of psychosis operationally.

The SOPS (Figure 1) consists of five Positive Symptom items,six Negative Symptom items, four Disorganization Symptom

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TANDY J. MILLER ET AL.

FIGURE 1. Scale of Prodromal Symptoms (SOPS).

277

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FIGURE 1. (Continued.)

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FIGURE 1. (Continued.)

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FIGURE 1. (Continued.)

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FIGURE 1. (Continued.)

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FIGURE 1. (Continued.)

TANDY J. MILLER ET AL. 283

FIGURE 1. (Continued.)

items, and four General Symptom items. Each item has a severityscale rating from 0 (Never, Absent) to 6 (Severe/Extreme—andPsychotic, for the positive items). The severity of the prodromalstate is judged according to the sum of the ratings from each ofthe SOPS items and ranges from 0 to 114. Thus, there are sever-ity ratings for the overall scale, each domain of pathology, as wellas individual items. The SIPS (available by request from the au-thors) includes 29 major probes organized according to each posi-tive symptom item in the SOPS. In the SIPS, patients are alsorated according to their Global Assessment of Functioning (19)(GAF), a DSM IV Schizotypal Personality Disorder criterionchecklist (20), and family history of mental illness. Diagnosis isaccomplished using the Criteria for Prodromal States (COPS,modeled after the criteria used by the Australians and outlinedabove). The SIPS is used to determine the presence or absence ofthe prodromal state, the type of prodromal state, and the presenceor absence of a psychotic state, and it includes the SOPS and theCOPS. The SOPS is used independently to determine the severityof the prodromal state once such a state has been diagnosed.

The diagnosis of a prodromal state in two of the Australian cat-egories is based on the development of positive symptoms. Posi-tive Symptom scores on the SOPS in the 1 to 2 range are consid-ered non-prodromal. Scores of 6 are considered psychotic. Scoresin the 3 to 5 range are considered at a prodromal level and wouldthen be evaluated according to the frequency criteria outlined inthe COPS to determine a diagnosis.

PRELIMINARY DATA

The PRIME Research Clinic has interviewed and identified 15 in-dividuals to date who are judged to be at risk for psychosis; of

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those, 10 have been randomized into the clinical trial. The avail-able means and standard deviations for all SOPS items of those13 meeting criteria an attenuated prodromal positive state aredepicted in Figure 2. Of the 10 randomized individuals, 3 haveconverted to psychosis. One male patient left the study prior tohis conversion, but allowed us to collect follow-along data. He de-veloped Bipolar Disorder. Of the other two individuals who con-verted, one woman, who converted to Schizophrenia, was admit-ted into the study with a total SOPS score of 44 and had anelevated total SOPS score of 56 upon conversion. The other sub-ject who converted had a total SOPS score of 58 upon admissionand a total SOPS score of 68 at the time of his conversion toSchizophrenia. In addition, one woman who was diagnosed as pro-dromal, after turning down participation in the study, went on toconvert to a frank schizophrenic psychosis. Although, very prelim-inary, our experience of rate of conversion appears to be consis-tent with that of the Australian investigators.

FUTURE DIRECTIONS

The SIPS and SOPS are recently developed instruments to servethe study and treatment of a new clinical population, the highrisk or pre-psychotic patient. Initial experience supports theirutility and validity. Future efforts are underway to refine anchorpoints for the Negative, Disorganized, and General domains ofpsychopathology and to demonstrate that inter-rater reliabilitycan be established.

REFERENCES

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